The structure of fibrinogen was studied. The covalent structure, including arrangements of disulfide bridges, of the NH2-terminal CNBr-fragment, N-DSK, has been completed. Studies on a number of plasmin and CNBr-fragments have provided information that allows us to align most of the chain structures in the fibrinogen molecule. These studies have shown that Fragment D is in close proximity to Fragment E in the B beta-chain and gamma-chains of these structures. Fragments containing the disulfide bonds outside N-DSK have been purified and partly characterized with regard to amino acid sequence. These disulfides are located in Fragment D and in a COOH-terminal fragment of the A alpha-chain. A method for quantitative determination of inhibition of binding of labeled N-DSK to Fbm-Sepharose has been worked out. Our studies have supported the notion that there are two binding domains in fibrinogen which participate in the fibrinogen-fibrin transition. One is in N-DSK and needs activation by thrombin and the other is located in Fragment D. A alpha 19 Arg and certain tyrosine residues appear to be important for binding. The immunological properties of chains and fragments of fibrinogen have been studied, in part with a radioimmunoassay for a COOH-terminal fragment of the A alpha-chain. The latter determinant, which is fully exposed in fibrinogen, is also present in serum. Experiments using thioredoxin for limited reduction of disulfide bonds have shown that certain bridges are crucial for function. Kinetic studies on the release of fibrinopeptide A by thrombin have shown that the structure A alpha 1-23 is crucial for thrombin binding and that the interaction is strengthened by A alpha 24-44. Fibrinopeptide B is only recognized by thrombin after polymerization of fibrinogen has started. Methods for assay of coagulation factors using substrates specific for Factor Xa and thrombin are being worked out. BIBLIOGRAPHIC REFERENCES: York, L.L. and Blomback, B.: Interaction of fragments of fibrinogen with insolubilized fibrin monomers (activated fibrinogen). Thrombosis Research, in press 1976. Kudryk, B., Blomback, B. and Blomback, M.: Fibrinogen Detroit - an abnormal fibrinogen with non-functional NH2-terminal polymerization domain. Thrombosis Research, in press 1976.